John Rinn, Marvin Caruthers Professor, University of Colorado Boulder BioFrontiers and Biochemistry
John Rinn, Marvin Caruthers Professor, University of Colorado Boulder BioFrontiers and Biochemistry
Biography
I am a professor and biotech founder focused on long noncoding RNAs (lncRNAs) — the part of the genome once thought of as “dark matter.” For the past 25 years, I have investigated how these RNAs control gene regulation, cell fate, and disease. My research has taken me from Yale and Stanford to Harvard, the Broad Institute, and now the University of Colorado Boulder. Today, as a founder of LincSwitch Therapeutics, I am working to translate this basic science into RNA therapies that can correct gene regulation at its source. Outside the lab, I find balance through my family as well as my love of ice hockey, hiking, and cycling.
Interview
NanoSphere: Tell us a bit about yourself—your background, journey, and what led you to where you are today.
John: I wasn’t the kind of kid who excelled in school—my focus was skateboarding, snowboarding, and hockey. I graduated high school with a 1.8 GPA and drifted through community college. An ACL injury changed everything: months of rehab in rural Georgia left me running up and down mountains, reading, and exploring science. I got a “D” on my first chemistry exam, but instead of being discouraged, I was hooked. Every mistake could be explained with logic and patience from my teacher. From that moment, I became dedicated to learning how to learn—and never received less than an A again in college. That passion to learn, pushed me to pursue graduate studies in Biochemistry and Biophysics. Along the way, I became fascinated by the genome itself — motivated by the simple question: how many genes are there, really? I focused my doctoral training solely to answer this question. The answer was even more fascinating that there are at least as many long noncoding RNA (lncRNA) genes as Protein genes. For the past 25 years I’ve been driven to understand how lncRNA genes work and currently how lncRNA may be leveraged to treat disease.
NanoSphere: You’ve helped define the field of lncRNA biology. What do you now see as the greatest barrier to realizing their therapeutic potential—targeting specificity, delivery systems, or functional validation?
John: This is a key question. I think delivery systems and targeting specificity are making great progress and facilitating therapeutic potential. The biggest barrier I see is functional validation. I have led numerous lncRNA functional validation studies, and it has never been straight forward – in my experience orthogonal approaches that triangulate to validate a function is the best approach.
NanoSphere: In building LincSwitch, how did you prioritize which lncRNAs to pursue therapeutically? Was disease mechanism clarity, expression pattern, or delivery tractability the key driver?
John: I wish it was all of the above, and I foresee a future where all these properties will be known for each lncRNA. We are developing a novel modality of RNA replacement therapies - so we want to de-risk as many other factors. Our strategy is to prioritize lncRNAs that upregulate disease genes with indications of unmet need and ease of delivery. Experience helps prioritize too; I have a long history with these genes which helps me see which pass a smell test.
John: I wish it was all of the above, and I foresee a future where all these properties will be known for each lncRNA. We are developing a novel modality of RNA replacement therapies - so we want to de-risk as many other factors. Our strategy is to prioritize lncRNAs that upregulate disease genes with indications of unmet need and ease of delivery. Experience helps prioritize too; I have a long history with these genes which helps me see which pass a smell test.
NanoSphere: As a scientist deeply rooted in lncRNA discovery, what was the biggest mindset shift you experienced when transitioning from academic research to launching a company focused on translating lncRNA biology into therapeutics?
John: I think I have had two mindset shifts since forming LincSwitch. First, was the change in perspective of focusing on a couple of lncRNAs at a time - to all lncRNAs at once. There are too few lncRNAs that have been studied compared to how many are known. I have a more wholistic lncRNA perspective now that requires scale and clever experimental and computational solutions. The second was the patient first mentality that I learned first-hand from the ReNU Syndrome United advocacy group. What do the families really need? What are the most attainable and most important first steps? These are now the questions that have transformed my mindset and in turn, drive.
John: I think I have had two mindset shifts since forming LincSwitch. First, was the change in perspective of focusing on a couple of lncRNAs at a time - to all lncRNAs at once. There are too few lncRNAs that have been studied compared to how many are known. I have a more wholistic lncRNA perspective now that requires scale and clever experimental and computational solutions. The second was the patient first mentality that I learned first-hand from the ReNU Syndrome United advocacy group. What do the families really need? What are the most attainable and most important first steps? These are now the questions that have transformed my mindset and in turn, drive.
NanoSphere: If there’s one key message or insight you’d like to share with readers about the future of RNA therapeutics, what would it be?
John: Biotech was founded on protein replacement therapies (insulin, erythropoietin, growth hormone etc) and is still expanding today. It naturally follows; this could extend to an RNA replacement modality. I envision a world where lncRNA therapies can restore, repair and rejuvenate gene circuits to augment human health and reverse disease and aging.
John: Biotech was founded on protein replacement therapies (insulin, erythropoietin, growth hormone etc) and is still expanding today. It naturally follows; this could extend to an RNA replacement modality. I envision a world where lncRNA therapies can restore, repair and rejuvenate gene circuits to augment human health and reverse disease and aging.
John`s references
- Personal Website
- CU Boulder BioFrontiers website
- Rinnformatics: Free Real World Bioinformatics Course for Genomics
- Timmerman Traverse Podcast
- https://podcasts.apple.com/us/podcast/the-long-run-with-luke-timmerman/id1282838969?i=1000661643771
- https://open.spotify.com/episode/12ft87QCI454TMC8toc0Xy
- https://player.fm/series/2396963/488214440